In vivo investigation of boron-rich nanodrugs for treating triple-negative breast cancers via boron neutron capture therapy

Lan, Kai-Wei; Huang, Wei-Yuan; Chiu, Yi-Lin; Hsu, Fang-Tzu; Chien, Yun-Chen; Hsiau, Yong-Yun; Wang, Tzu-Wei; Keng, Pei Yuin

doi:10.1016/j.bioadv.2023.213699

Cited by 3 publications

(5 citation statements)

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“…The in vitro BNCT experiments were performed at the Tsing Hua Open-pool Reactor (THOR) following established protocols in the literature. − In a typical experiment, 3 × 10 5 B16–F10 melanoma cells per well were suspended in 2 mL of DMEM and seeded in a 6-well plate. After a 24-h incubation period, the cells were treated with either 1 mg/mL of the reconstructed micelle solution, prepared using DMEM, or a 1 mg/mL BPA solution, which were prepared by diluting a stock solution of 25 mg/mL BPA in DMEM.…”

Section: Methodsmentioning

confidence: 99%

Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies

Fu,

Chiu,

Huang

et al. 2024

Biomacromolecules

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Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but requires a selective and high B-10 loading boron drug. This manuscript investigates boron-rich poly(ethylene glycol)-block-(poly(4-vinylphenyl boronate ester)) polymer micelles synthesized via atom transfer radical polymerization for their potential application in BNCT. Transmission electron microscopy (TEM) revealed spherical micelles with a uniform size of 43 ± 10 nm, ideal for drug delivery. Additionally, probe sonication proved effective in maintaining the micelles' size and morphology postlyophilization and reconstitution. In vitro studies with B16−F10 melanoma cells demonstrated a 38-fold increase in boron accumulation compared to the borophenylalanine drug for BNCT. In vivo studies in a B16−F10 tumor-bearing mouse model confirmed enhanced tumor selectivity and accumulation, with a tumor-to-blood (T/B) ratio of 2.5, surpassing BPA's T/B ratio of 1.8. As a result, mice treated with these micelles experienced a significant delay in tumor growth, highlighting their potential for BNCT and warranting further research.

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Section: Methodsmentioning

confidence: 99%

Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies

Fu,

Chiu,

Huang

et al. 2024

Biomacromolecules

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“…After the incubation period, the cells were rinsed twice with PBS, and the 96-well plates were placed onto a custom-made acrylic holder covered with a PE board. The PE board was utilized to decelerate the neutron flux to achieve a higher proportion of epithermal neutrons (0.5 eV to 10 keV) for neutron irradiation [ 26 ]. The neutron irradiation was conducted at a flux of 1 × 10 9 neutrons/cm 2 ⋅s and an irradiation power of 1.2 MW for 30 min, following our previous studies [ 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…The PE board was utilized to decelerate the neutron flux to achieve a higher proportion of epithermal neutrons (0.5 eV to 10 keV) for neutron irradiation [ 26 ]. The neutron irradiation was conducted at a flux of 1 × 10 9 neutrons/cm 2 ⋅s and an irradiation power of 1.2 MW for 30 min, following our previous studies [ 25 , 26 ]. Following neutron irradiation, the cells were further incubated for 24 h and 48 h. Subsequently, 10 μl of MTS assay was added to each well and the plate was incubated for an additional 2 h. The absorbance was measured at a wavelength of 490 nm using a spectrometer to determine the cell viability after BNCT treatment.…”

Section: Methodsmentioning

confidence: 99%

“…Before neutron irradiation, the mice were anesthetized intraperitoneally with 0.04 ml of Zoletil/Rompun cocktail (mixing ratio with Zoletil [50 mg/ml]/Rompun [23.32 mg/ml] = 1:4). The mice were irradiated with neutron irradiation at a flux of 1 × 10 9 neutrons/cm 2 ⋅s and an irradiation power of 1.2 MW for 30 min following our previous studies [ 25 , 26 ]. The mice were removed from the irradiation chamber and placed into a cage to allow the mice to recover from anesthesia.…”

Section: Methodsmentioning

confidence: 99%

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Enhancing Cancer Therapy: Boron-Rich Polyboronate Ester Micelles for Synergistic Boron Neutron Capture Therapy and PD-1/PD-L1 Checkpoint Blockade

Chiu,

Fu,

Huang

et al. 2024

Biomater Res

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Malignant cancers, known for their pronounced heterogeneity, pose substantial challenges to monotherapeutic strategies and contribute to the risk of metastasis. Addressing this, our study explores the synergistic potential of combining boron neutron capture therapy (BNCT) with immune checkpoint blockade to enhance cancer treatment efficacy. We synthesized boron-rich block copolymer micelles as a novel boron drug for BNCT. Characterization was conducted using nuclear magnetic resonance, gel-permeation chromatography, transmission electron microscopy, and dynamic light scattering. These micelles, with an optimal size of 91.3 nm and a polydispersity index of 0.18, are suitable for drug delivery applications. In vitro assessments on B16-F10 melanoma cells showed a 13-fold increase in boron uptake with the micelles compared to borophenyl alanine (BPA), the conventional boron drug for BNCT. This resulted in a substantial increase in BNCT efficacy, reducing cell viability to 77% post-irradiation in micelle-treated cells, in contrast to 90% in BPA-treated cells. In vivo, melanoma-bearing mice treated with these micelles exhibited an 8-fold increase in boron accumulation in tumor tissues versus those treated with BPA, leading to prolonged tumor growth delay (5.4 days with micelles versus 3.3 days with BPA). Moreover, combining BNCT with anti-PD-L1 immunotherapy further extended the tumor growth delay to 6.6 days, and enhanced T-cell infiltration and activation at tumor sites, thereby indicating a boosted immune response. This combination demonstrates a promising approach by enhancing cytotoxic T-cell priming and mitigating the immunosuppressive effects of melanoma tumors.

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“…Boron carbon oxynitride (BCNO) is another family of boron nitride, which is a non-toxic and earth-friendly phosphor with application in high contrast cellular imaging and toxic metal sensors. Lan et al prepared a polyethylene-glycol-coated boron carbon oxynitride nanoparticle (PEG@BCNO), it showed better therapeutic performance in animal models than that of 10 BPA 66 . Besides PEG@BCNO, Chiang et al coated BCNO with polyethyleneimine (PEI), the PEI@BCNO exhibited higher boron content of 48μg B/g of tumor cell, while PEG@BCNO only reached 16μg 10 B/g of tumor cell in in-vitro studies (Figure 7 D) 67 .…”

Section: Boron-containing Nct Nanomedicinementioning

confidence: 99%

Recent progress of nano-drugs in neutron capture therapy

Zhou,

Cheng,

Liu

et al. 2024

Theranostics

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As a developing radiation treatment for tumors, neutron capture therapy (NCT) has less side effects and a higher efficacy than conventional radiation therapy. Drugs with specific isotopes are indispensable counterparts of NCT, as they are the indespensable part of the neutron capture reaction. Since the creation of the first and second generations of boron-containing reagents, NCT has significantly advanced. Notwithstanding, the extant NCT medications, predominantly comprised of small molecule boron medicines, have encountered challenges such monofunctionality, inadequate targeting of tumors, and hypermetabolism. There is an urgent need to promote the research and development of new types of NCT drugs. Bio-nanomaterials can be introduced into the realm of NCT, and nanotechnology can give conventional medications richer functionality and significant adaptability. This can complement the advantages of each other and is expected to develop more new drugs with less toxicity, low side effects, better tumor targeting, and high biocompatibility. In this review, we summarized the research progress of nano-drugs in NCT based on the different types and sources of isotopes used, and introduced the attempts and efforts made by relevant researchers in combining nanomaterials with NCT, hoping to provide pivotal references for promoting the development of the field of tumor radiotherapy.

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In vivo investigation of boron-rich nanodrugs for treating triple-negative breast cancers via boron neutron capture therapy

Cited by 3 publications

References 92 publications

Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies

Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies

Enhancing Cancer Therapy: Boron-Rich Polyboronate Ester Micelles for Synergistic Boron Neutron Capture Therapy and PD-1/PD-L1 Checkpoint Blockade

Recent progress of nano-drugs in neutron capture therapy

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